Kim Yoonhee, Doan Betty Q, Duggal Priya, Bailey-Wilson Joan E
Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, Maryland 21224, USA.
BMC Proc. 2007;1 Suppl 1(Suppl 1):S152. doi: 10.1186/1753-6561-1-s1-s152. Epub 2007 Dec 18.
"Genetical genomics", the study of natural genetic variation combining data from genetic marker-based studies with gene expression analyses, has exploded with the recent development of advanced microarray technologies. To account for systematic variation known to exist in microarray data, it is critical to properly normalize gene expression traits before performing genetic linkage analyses. However, imposing equal means and variances across pedigrees can over-correct for the true biological variation by ignoring familial correlations in expression values. We applied the robust multiarray average (RMA) method to gene expression trait data from 14 Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees provided by GAW15 (Genetic Analysis Workshop 15). We compared the RMA normalization method using within-pedigree pools to RMA normalization using all individuals in a single pool, which ignores pedigree membership, and investigated the effects of these different methods on 18 gene expression traits previously found to be linked to regions containing the corresponding structural locus. Familial correlation coefficients of the expressed traits were stronger when traits were normalized within pedigrees. Surprisingly, the linkage plots for these traits were similar, suggesting that although heritability increases when traits are normalized within pedigrees, the strength of linkage evidence does not necessarily change substantially.
“遗传基因组学”，即将基于遗传标记的研究数据与基因表达分析相结合来研究自然遗传变异，随着先进微阵列技术的最新发展而迅速兴起。为了解决微阵列数据中已知存在的系统变异问题，在进行遗传连锁分析之前对基因表达性状进行适当的标准化至关重要。然而，通过忽略表达值中的家族相关性，对各个家系强制设定相等的均值和方差可能会过度校正真实的生物学变异。我们将稳健多阵列平均（RMA）方法应用于GAW15（遗传分析研讨会15）提供的来自14个犹他州人类多态性研究中心（CEPH）家系的基因表达性状数据。我们将使用家系内样本池的RMA标准化方法与使用单个样本池中的所有个体（忽略家系成员关系）的RMA标准化方法进行了比较，并研究了这些不同方法对先前发现与包含相应结构基因座区域连锁的18个基因表达性状的影响。当家系内对性状进行标准化时，表达性状的家族相关系数更强。令人惊讶的是，这些性状的连锁图谱相似，这表明尽管当家系内对性状进行标准化时遗传力会增加，但连锁证据的强度不一定会有实质性变化。
